Materials for Improved Wear Resistance of Total Artificial Joints

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Objectif

A. BACKGROUND

Approximately two million artificial joints are implanted in patients every year, with a commercial value of well over two billion. A significant proportion of these joint prostheses are manufactured in Europe. The short to medium term performance of artificial joints is good, but long-term failure is due to adverse biological reactions to the wear particles. The cost of operations in Europe is estimated at ten billion per year, and over ten percent of these are for revision of worn and failed prostheses. Equally, the implications of high wearing or failed implant materials are severe as indicated by recent UK Government Health advisory warnings on zirconia ceramics and Hylamer polyethylene. Hence there are considerable political, economic, social and technical reasons to improve the wear performance of biomaterials used in Joint Replacements. With increasing number of young patients requiring joint replacements, and increasing lifetime of the elderly population, the performance requirements, the expected lifetimes and the number of artificial joints implanted is increasing markedly.

Historically, new bearing materials were 'tried out' in patients, the consequence of incorrect design and material selection and subsequent failure now means that there are extensive pre-clinical requirements for evaluation of materials prior to implantation. This is by no means a simple problem, environmentally (biochemical) conditions in the body are harsh, biomechanical requirements are complex and variable, and the biological response to wear particles is largely unknown and dependent on the genetic profile of the recipient. Biotribology is a highly multidisciplinary subject crossing engineering materials and physical science, biological science and medicine. Predicting the mechanical and tribological performance of improved bearing surfaces, and understanding the biological responses to wear debris and the resulting potential clinical outcomes, remains a substantial scientific and technological challenge.

There is currently considerable interest in a range of new materials, polymers, metals and ceramics and new designs of artificial joints to reduce wear. Key factors limiting the successful development of improved products are our limited understanding of biotribological science, the capability and capacity to simulate in vivo conditions in the laboratory in pre-clinical tests, and a lack of fundamental understanding of the complex and heterogenous biological reactions and biocompatibility of wear debris in the body.

Research and pre-clinical studies of the biotribology of artificial joints are primarily carried out in hip and knee joint simulators. Although there are over 200 different types of prostheses currently implanted, with each type having approximately 5 to 10 different sizes and configurations, there are currently less than 100 stations of hip joint simulators and less than 50 stations of knee joint simulators in Europe. Only six institutions, three Government and three industrial have a capacity greater than 10 stations. As it can take up to one year to test a particular implant and multiple replicates n = 5 to 10 are ideally required, the capability and capacity to carry out work in this area is limited. There are a greater number of institutions (10 to 20) with much smaller capacity and experience. There is an extensive range of medical and biomaterials companies involved in manufacture of artificial joints requiring information from these simulation systems and a very long list of customers (surgeons and patients) requiring knowledge about potential clinical performance.

It is estimated that there will be a network of 200 researchers, including institutes as well as industrial users and clinical users who will form an integrated supply chain for these products.

B.OBJECTIVES AND BENEFITS

Objectives

The main objective of the Action is to develop materials for improved wear resistance of artificial joints and novel low wearing designs. For this purpose, the biotribology of materials in artificial hip and knee joints, the mechanisms of lubrication and wear, the methods of in vitro simulation and testing, and the resulting biocompatibility and biological reactions to the wear products will be investigated in order to contribute to the standradising of in vitro simulation and testing. This development will furthermore result in reduced wear particles, lower adverse biological reactions and longer lifetimes of artifical joints and natural joints.

Benefits

Sharing a rapidly developing field of knowledge and understanding will improve the international competitiveness of the European research base in an environment where there is a strong North American activity.

Development of a common understanding of basic test methods will improve the development of ISO standards.

Dissemination of knowledge to smaller and emerging research groups in biotribology will enhance our long term research capacity in the field.

Dissemination to over 100 industrial users and material suppliers, will enhance our core technical and commercial capability and underpin the EU manufacturing base in this area in which we are a net exporter.

Dissemination to over 100 medical user groups will improve selection of implants for different patient groups, and help define future needs for product development.

New scientific knowledge about biomaterials and improved in vitro test methodologies will enhance and accelerate new product developments and their introduction into clinical studies.

C. SCIENTIFIC PROGRAMME

The scientific programme will focus on four themes described below. Collaborative and multi centre interdisciplinary research studies are required to address these areas of knowledge and technology transfer. Security e.g. biocompatibility, environmental e.g. toxicity and ethical aspects are taken into account.

C.1Enhanced and crosslinked polyethylenes in artificial hip joints

Stabilised and crosslinked polyethylenes have been developed and introduced clinically over the last five years. These materials are more stable than the previously used polyethylenes, which were prone to oxidation after irradiation in an oxygen containing environment. There is a clear indication that as the level of crosslinking is increased the wear volume can decrease and there are currently a range of materials with different levels of crosslinking being used clinically.

There is a number of factors which influence the choice of level of crosslinking. The reduction in wear with crosslinking is dependent on kinematic conditions of the bearing, and this varies between patients and simulation systems. As the size of the femoral head increases, the sliding distances increase and this implies the need for a lower wearing crosslinked polyethylene. However this also implies thinner bearing materials and elevated stress levels which may adversely affect lifetime.

Equally, as crosslinking increases the fracture toughness and fatigue life of the polyethylene reduces and has significant constraints on design and lifetime. Although all the materials are more stable than previously used polyethylenes, there is currently little understanding as to how different crosslinking and thermal treatments influence oxidation resistance.

The major uncertainty surrounding the level of crosslinking relates to the morphology of the wear particles and resulting biological reactions and biocompatibility. There is some evidence that as the level of crosslinking increases the wear particles (or a greater percentage of them) become smaller. Recent cell and biocompatibility studies indicate that this may lead to elevation of the inflammatory response and osteolytic reaction. Collaborative research studies are needed to investigate the performance of different crosslinked polyethylenes. These will include comparative tests and round robin studies in wear and hip joint simulators.

Some of the uncertainty about the relative performance of crosslinked polyethylenes relates to deficiencies in basic understanding of the biotribology of these systems. In particular, knowledge of how key tribological variables influence wear, wear debris and osteolysis in crosslinked polyethylenes is lacking and this frequently leads to studies being carried out under different and

inappropriate conditions, and results in conflicting and contradictory results. While it is understood that crosslinking improves wear, through resistance to cross shear, quantitative relationships between kinematic input conditions, amount of cross shear and wear rates for crosslinked polyethylenes are not known. At present materials are investigated and pre-clinically evaluated under different kinematic conditions. The understanding of the effect of kinematic conditions on wear will influence the definition of standards for simulators.

The lubrication conditions that occur in the body (both amount and concentration of lipids and proteins) are quite variable. Additionally, the concentration levels used in laboratory simulation vary by up to fourfold. There are concerns that the use of artificially high serum, protein and lipid concentrations will produce artefactually lower wear rates for crosslinked polyethylenes. This may well lead to inappropriate designs and clinical applications.

The understanding of the influence of head size and geometry on wear of crosslinked polyethylenes remains uncertain. As head size increases, sliding distance increases and this elevates wear in conventional polyethylenes. However, crosslinked polyethylenes may benefit from enhanced mixed and hydrodynamic lubrication which may reduce wear with larger head sizes. The optimum head size for crosslinked polyethylene remains to be determined. Additionally, different femoral head materials, cobalt chrome alloys, stainless steel alloys as well as alumina ceramic and ceramic matrix composites will be studied.

Adverse tribological conditions occur in vivo which can accelerate wear. These include third body particles and damage, joint laxity, separation and rim contact. Fundamental polymer tribology indicates that as the toughness of the material is reduced its wear resistance in an abrasive environment is reduced. The influence of third body femoral damage and third body particles on wear remain to be fully determined. Additionally, joint laxity, separation and head rim contact occurs in many patients in vivo, and the effects of these tribological conditions on wear of crosslinked polyethylene is not known.

C.2Alternative hard bearing couples for artificial hip joints

The identification of polyethylene wear debris induced osteolysis in hip arthroplasty has led to the development and clinical introduction of a number of alternative hard on hard bearing couples such as metal on metal, ceramic on ceramic, ceramic matrix composites and surface engineered metal bearings. Basic laws of wear indicate that increases in hardness of the material will reduce wear, and generally speaking, all of the hard on hard materials have lower wear rates than polyethylene. However, there still remain many uncertainties about their long term clinical performance. In particular, metal on metal bearings comprising CoCr allow generation of fine wear particles and elevated ion levels, and there is interest in reducing the wear of these bearings further. Surface engineering approaches offer an interesting perspective. In alumina ceramic bearings the fracture toughness remains a concern and a design constraint, and rim contact and dislocation may accelerate wear. New ceramic matrix composites that have improved toughness offer considerable potential. Although these hard on hard bearings are less compliant to changes in surgical technique, and patient activity, there is a need to understand the conditions under which these may not perform optimally and address this through design improvements. Further research studies, both in vitro and in vivo, are needed to understand the tribological performance of alternative bearing couples. In particular it is important to understand the relationships between tribological and material conditions and wear mechanisms, and debris generation.

Wear debris and its biocompatibility is critically important in these alternative bearing couples. Generally the wear particles are much smaller than polyethylene, less than 100 nm in size and this demands new methods for analysis and characterisation. Conventional light and scanning electron microscopy, atomic force microscopy and scanning probe microscopy need to be applied to both the wear particles and wear surfaces at the nanometre scale.

These wear particles generate additional biological concerns, metal ion release and its influence on cell viability. Cytotoxity and tissue necrosis remain major issues, and requires further in vitro biocompatibility studies on real wear debris rather than just the bulk materials. Surface physics and chemistry of these nanometre size particles and the resulting biomolecular attachments controling

these biological processes will be investigated. Variations in the biological response of the population, the role of metal ion sensitivity, genetic predisposition and potential for genetic transformation require focused research studies. These smaller particles may also cause inflammation and osteolysis, and the release of inflammatory cytokines by particles less than 100 nm in size needs to be investigated.

There are a range of tribological variables that control wear in these hard on hard bearings. This quantitative relationship of the effect of these variable on wear remain to be determined and should be the focus of future in vitro simulator tests. These variables include geometrical design, head size and radial clearance and manufacturing tolerance of sphericity and surface roughness. These parameters are important in determining the lubricating capacity of the bearing. In particular, the potential for increasing the head diameter and moving the lubrication regime towards the fluid film end of the mixed regime has still to be fully exploited. These bearings, in particular metal on metal, may well be sensitive to the biochemistry of lubricant and the role of protein concentration of wear needs to be determined.

Surgical parameters such as cup position and joint laxity can lead to less than ideal bearing configuration and in particular, head rim contact. The influence of this on wear of the bearings will be investigated through in vitro simulations.

Ceramic and ceramic-like coatings have low fracture toughness and the rate of brittle fracture failure mechanisms and also intergranular surface fracture wear mechanisms need to be further investigated in order to provide guidelines for failure analysis and risk assessment.

C.3Wear of polyethylenes in artificial knee joints

Polyethylene is used extensively as the tibial bearing surface in artificial knee joints, articulating against cobalt chrome alloy femoral condyles. Unlike the hip, where many alternative materials to polyethylene are being introduced, polyethylene remains the primary bearing surface in the knee. The long term concerns about polyethylene wear debris induced osteolysis remain and there is considerable demand to reduce the polyethylene wear and wear debris in the knee. The knee is a more complex bearing than the hip and many design variables as well as material variables can influence the performance. Additionally the knee is a higher contact stress bearing and hence durability and fatigue of polyethylene are more important.

Crosslinking of polyethylene has been shown to reduce volume wear in the hip, but in the knee its benefits have still to be established. Studies are required to understand the effect of crosslinking in the knee, on wear under different kinematic conditions, and in particular, establish the role of surface pitting wear, when the crosslink density increases, and the fatigue and toughness of the polyethylene is reduced.

Higher molecular weight polyethylenes have also been developed, as their increased molecular weight has been proposed to reduce wear. However, the reduction in toughness and the potential for producing smaller and more biologically active wear particles is of concern and will be the focus of laboratory simulator investigations.

In the knee most femoral counterface are manufactured from cobalt chrome alloys and these are damaged and scratched in vivo by third body particles, which lead to acceleration of polyethylene wear. In the hip monolithic ceramics are used as the femoral counterface to improve hardness and resistance to damage, and the net effect is a reduction in polyethylene wear. In the knee monolithic ceramics are not available, but surface modification and coatings are under development and there is considerable potential to investigate the use of surface engineered solutions to reduce wear.

Polyethylene wear has also been identified on the underside of the tibial insert where it is fixed to the metallic tibial tray. Many trays are manufactured from titanium alloys and wear accelerated corrosion is a key factor in this system. To identify the quantity of this wear, the influence of fixation designs and also the role of surface coatings was not possible so far and requires thus further investigation.

There are currently two fundamentally different types of knee designs, fixed bearings and mobile bearings which allow articulation of the mobile polyethylene tibial insert at the tibial counterface as well as the femoral counterface. There are contradictory arguments relating to the benefits of mobile bearing designs. Proponents indicate lower contact stresses extend the fatigue life while others indicate larger bearing areas increase wear. Recently it has been discovered that decoupling rotational motion to the tibial interface simplifies motion on the femoral articulation and reduces wear. This phenomena requires further investigation in different types of mobile bearing knees.

The geometrical design of the tibial and femoral surfaces results in considerable variation in the resulting range of motion and contact areas and stresses in different types of design. This can influence both the fatigue life and wear of knees. Extensive simulator studies are required to investigate the effect of different geometries and these should be correlated with wear and failure of explanted prostheses.

Wear of knee prostheses have been primarily studied under a standard set of walking conditions. Flouroscopic studies have shown that kinematics change considerably between patients and between different types of activities. The influence of variations in kinematics and activities on wear have not yet been established. Knee simulator studies are required to investigate the effect of different degrees of rotation and translation and the influence of lateral femoral condylar lift off on wear. Additionally the effect of surgical procedures such as malalignment, vagus-valgus tilt and contact mechanics will be investigated.

C.4Therapies and treatments to extend the life of the natural jointLubrication and wear reduction therapies

There is increasing interest in lubrication therapies that can be delivered to diseased or degenerative natural synovial joints which can delay the requirement for a total joint replacement. Boundary lubrication materials, such as hyaluronic acid, glycoaminoglycans GAGS, and phospholipids are currently being delivered clinically or under consideration as potential therapies. The mechanism by which these materials relieve pain and provide effective boundary lubrication are not fully understood. Although each element contributes to the lubrication of the healthy synovial joint, their effectiveness as a boundary lubricant in cartilage degeneration grades II, III and IV remains unclear. Development of an understanding of boundary lubrication mechanisms is essential for designing treatment regimes for existing material and for development of improved formulation. Laboratory simulation of friction and wear need to be established with both natural and degenerative articular cartilage.

Tissue matrix substitution

When cartilage degeneration and defects are severe (Grade IV) and remain finite in size, there is a potential to repair with matrix substitution materials either as a synthetic implant or as a scaffold for biological regeneration. A number of these potential solutions are currently proposed such as biological matrices, synthetic hydrogels, hyaluronic acid networks, polyurethanes, alginate gels. The physical properties of these scaffolds vary considerably to those of natural articular and to date there has been little understanding of the tribological performance of these replacement matrices. In vitro models of repaired degenerative cartilage will be established and friction lubrication and wear investigated when articulating against healthy articular cartilage. This will allow recommendation for the improvement of cartilage matrix substitution materials.

D.Organisation

The scientific programme will consist of four working groups. Each working group will have five different themes or areas of work.

The Working Group meetings will involve partners plus invited experts, in which the progress of the work programme will be discussed, current knowledge and information will be exchanged, current problems and issues brainstormed and a consensus on current state of the art knowledge reached. This will then be disseminated and discussed more widely in workshops and publications. Web sites will be established for common information, presentation and reference materials. Additional partners will join the Working Groups throughout the programme.

Short Term Scientific Missions of young researchers will be widely used to strengthen the interdisciplinary cooperation.

Also, through close contact with the Technical Committee on Materials and the Ad hoc Group on Biomaterials - i.e. to all relevant COST domains - interdisciplinary issues, including ethical aspects, are dealt with properly.

E. TIMETABLE

The overall programme will last five years, due to necessary extensive experimental and theoretical studies in order to achieve the main objective of the Action "...to contribute to the standardising of in vitro simulation testing". The mechanical, chemical and biocompatibility testing, the resulting modifications and the following testing require a five year period.

F. ECONOMIC DIMENSION

The market for joint replacement is currently two Billion Euro per year. The cost of delivering these therapies to the patients is at least ten-fold that value. The following COST countries have actively participated in the preparation of the Action or otherwise indicated their interest:

AustriaGermanyIrelandItalySpainSwitzerlandUnited Kingdom

On the basis of national estimates provided by the representatives of these countries, the economic dimension of the activities to be carried out under the Action has been estimated, in 2002 prices, at roughly Euro 10 million.

This estimate is valid under the assumption that all the countries mentioned above but no other countries will participate in the Action. Any departure from this will change the total cost accordingly.

G. DISSEMINATION PLAN

In each of the four Working Groups, collaborative programmes of work will be established in each of the theme areas between the partners. Working Group meetings will bring together the results of these studies, providing a vehicle to reporting state of the art consensus statements on these critical issues. Work will be carried out in a precompetitive framework to allow sharing and dissemination of knowledge to and from industrial and academic research centres. Dissemination will take place through workshops which will involve research representatives, over 100 material and industrial suppliers and 100 medical users. Publications and presentations at international conferences will also contribute to the dissemination.

Also close contacts to national and international scientific organisations like e.g. the European Society for Biomaterials (ESB) will be established for the dissemination of achievements - and for the visibility of COST 533.